Efficacy and Mechanism of Preoperative Simvastatin Therapy on Myocardial Protection after Extracorporeal Circulation

Abstract

Background. Cardiopulmonary bypass (CPB) causes systemic inflammatory response and ischemia-reperfusion (IR) injury. Objective. To investigate the effect and mechanism of simvastatin on myocardial injury in cardiac valve surgery with CPB. Methods. One hundred thirty patients were randomly assigned to the statin group (n=65) or control group (n=65). Simvastatin was administered preoperatively and postoperatively. Duration of intensive care unit stay, duration of assisted ventilation, and left ventricular ejection fraction were recorded. Plasma was analysed for troponin T (cTnT), isoenzyme of creatine kinase (CK-MB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Ultrastructure of the myocardium and autophagosomes were observed. Beclin-1, LC3-II/I, P62, AMPK, and the phosphorylation of AMPK in cardiomyocytes were detected. Results. Simvastatin significantly reduced the duration of assisted ventilation (P=0.030) and ejection fraction was significantly higher in the statin group (P=0.024). Simvastatin significantly reduced the levels of cTnT, CK-MB, TNF-α, IL-6, and IL-8 (P<0.05), reduced the expression of LC3-II/LC3-I and Beclin 1, and increased the expression of phosphorylation of AMPK. Simvastatin reduced the generation of autophagosomes and the ultrastructural injuries to myocardium. Conclusion. Perioperative statin therapy reduced myocardial injury by regulating myocardial autophagy and activating the phosphorylation of AMPK. The registration number of this study is ChiCTR-TRC-14005164.